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Biomedical subjects

H M Frost

Publications and source records attributed to H M Frost.

At least 19 recordsLinked to original sources
PubMed1992

The role of changes in mechanical usage set points in the pathogenesis of osteoporosis.

Mechanical usage (MU) effects on modeling drifts and BMU-based remodeling affect bone mass in defined ways. Decreased MU stops additions of bone by modeling and increases removal of bone next to marrow by remodeling. The latter effect thins cortices and reduces trabecular number, thickness, and connectivity. Return to normal MU makes remodeling begin conserving existing bone and leaves modeling still off. Hypervigorous MU can make modeling increase bone mass during growth and makes remodeling keep conserving it in children and adults. These effects can be said to begin when typical bone strains rise through two threshold ranges, one for remodeling and a higher one for modeling. Raising the thresholds while normal MU continues should give bone a spurious disuse message, whereupon disuse effects would begin. The bone anatomic and tissue dynamic patterns in acute and chronic disuse resemble those seen in developing and acquired postmenopausal osteoporosis and in other forms of osteoporosis, too. If some hormones, drugs, and other agents increase those thresholds, this could explain such similarities.

Biomechanical Phenomena↗
PubMed1992

On the rat model of human osteopenias and osteoporoses.

The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

Adult↗
PubMed1992

Perspectives: bone's mechanical usage windows.

As mechanical usage (MU) of a bone changes from complete disuse towards maximal vigor, the biologic mechanisms that can adapt it to its MU tend to react predictably. Acute disuse can increase BMU (Basic Multicellular Unit, the remodeling 'packet') creations but reduces how much bone they form, to increase bone loss next to marrow. Normal usage reduces those creations to normal and tends to equalize their resorption and formation; this conserves bone. In mild overloading, BMUs still conserve existing bone, while modeling drifts can begin adding to and/or reshaping it. Severe overloading can increase microdamage alarmingly, its repair by BMUs too, and can cause woven bone formation, anarchic resorption and a regional acceleratory phenomenon. Those ranges of MU vigor can define four 'windows'. An adapted window should apply to healthy, normally active adult mammals, and a mild overload window to healthy, normally active growing ammals. The biologic responses in the pathologic window could explain among other things some total joint and internal fixation failures, some pathologic fractures and some bone healing and sports medicine problems.

Adaptation, Physiological↗
PubMed1991

A new direction for osteoporosis research: a review and proposal.

This article suggests why drugs that only reduce the activity of existing osteoclasts or enhance the activity of existing osteoblasts probably cannot cure the osteopenias associated with most osteoporoses. Instead they should add only limited amounts of bone, which should begin to disappear after treatment stops. That behavior depends on these facts. Different threshold ranges of mechanical bone strains control gains and losses of bone mass. One threshold controls gains by modeling drifts, and a lower one controls losses by remodeling BMUs. A drug that does not change those thresholds should limit gains (or losses) of bone during indefinitely continued treatment. Success in curing those osteopenias should require learning how to change the thresholds.

Biomechanical Phenomena↗
PubMed1990

Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem.

From the nature of a bone's endload and its local surface strains, the theory computes a modeling operator, Gamma (gamma), that predicts whether mechanical factors will cause lamellar bone modeling drifts, and where and of what kind. A given mechanical bone strain history then provides a separate modeling rate function, M, to specify the rate of such modeling drifts as fractions of the largest possible ones. Multiplying the two functions, e.g., gamma.M, then predicts mechanically controlled bone modeling responses for cortical and trabecular bone, both quantitatively and qualitatively. The theory correctly predicts each of the 6 known "principal adaptations" of lamellar bone, which provide a critical test of any such theory for this organ. The theory accounts for biologic, biomechanical, and clinical-pathologic knowledge not available in Wolff's time nor accounted for by most biomechanicians since. Existing proven methods can provide all numerical data needed to satisfy the theory's mathematical equations and already suggest provisional values for most of them. Its originator views the theory as the kernel of more and better theories to come rather than a finished work, a kernel that suggests a new and in some respects novel logical framework for analysing the problems, and a kernel that invites critique, refinement, and/or exploitation by others.

Adaptation, Physiological↗
PubMed1990

Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff's law: the remodeling problem.

Basic multicellular unit (BMU)-based remodeling of lamellar bone causes bone turnover, net gains and losses of bone on some bone surfaces or "envelopes," and a remodeling space comprising bone temporarily absent due to evolving resorption spaces and incomplete refilling of them by new bone. Those features depend a) on how many new BMU arise annually, b) on how much bone each BMU has resorbed and c) formed upon its completion, and d) on how long the typical BMU takes to become completed. Because a, b, and c have limiting or maximal values in life that direct and/or indirect effects of mechanical usage of the skeleton can change, the theory presented here derives mechanical usage functions that express what fractions of those maxima a given mechanical usage history allows to happen. The theory predicts some changes in bone formation, resorption, balance, turnover, and remodeling space that depend on how remodeling responds to the vigor of a subject's mechanical usage. The theory can predict specific effects of specific mechanical challenges that experiments can test, and it fits abundant published evidence. As the kernel of a new approach to the problem it awaits critique and refinement by others. It plus the 3-way rule can redefine Wolff's law conceptually and also in mathematical and quantifiable form.

Adaptation, Physiological↗
PubMed1990

Skeletal structural adaptations to mechanical usage (SATMU): 3. The hyaline cartilage modeling problem.

A chondral growth/force response curve predicts how intact hyaline cartilage plates grow in vivo under typical peak mechanical unit loads and gradients thereof in healthy immature mammals. Growth under tension would increase as tension rises from zero to a level that damages the tissue. Under compression, growth would increase as the load rises from zero to a level at which growth becomes maximal (the growth-ascending limb of the curve). Further increases in compression loads retard growth and large enough increases can stop it entirely (the growth-descending limb of the curve). For equal changes in loads, the smallest growth change would occur under tension; the largest change would occur on the growth-descending part of the curve. Under zero load a respectable "baseline growth" still occurs. Those effects are superimposed on inherent differences in growth potential of different chondral plates, differences that are determined partly in utero and by the genome. The curve's features can explain many anatomical facts, including the ball-and-socket ankle, joint alignment in the valgus-varus sense, hip dislocations in spasticity, different epiphyseal heights, short bones in paralysed limbs, long bone overgrowth after fractures, why some joint surfaces remain concave and others convex throughout growth, and why some growth plates are domed instead of flat. The above phenomena can be expressed mathematically, and a phenomenologic basic logical framework for doing that is suggested.

Adaptation, Physiological↗
PubMed1990

Skeletal structural adaptations to mechanical usage (SATMU): 4. Mechanical influences on intact fibrous tissues.

This paper proposes that the growth in length of living fibrous tissue structures (tendon, ligament, fascia) responds primarily to circulating systemic rather than mechanical factors. However, growth of the thickness of those structures responds primarily to their mechanical tension loads in the special sense that, when the tissue's typical peak mechanical strains exceed a threshold value, its cells begin to add new collagen to increase its thickness, strength, and tension stiffness. When subsequent peak strains reduce to the threshold value, then further additions of collagen stop. That process defines mechanically controlled modeling of fibrous tissues. The collagen in these tissues can also develop mechanical microdamage (MDx) under repeated tension load-deload cycles. Special maintenance mechanisms normally repair that MDx to prevent accumulations that would threaten structural integrity. As a result, spontaneous complete ruptures of these structures can happen when MDx production exceeds its repair. These maintenance mechanisms also prevent gradual stretching under continuous tension loads, a process the author suggests calling creep compensation. When the creep compensation mechanism becomes incompetent, structures can stretch under continuous loads; when it becomes overactive, contractures can occur. The above meld of fact and inference provides the kernel of a general theory for the responses of the architecture and mechanical competence of intact fibrous tissues to mechanical usage.

Adaptation, Physiological↗
PubMed1989

Transient-steady state phenomena in microdamage physiology: a proposed algorithm for lamellar bone.

This algorithm suggests that in steady states the momentary burden of unrepaired microdamage (MDx) in lamellar bone equals the rate of creation of new MDx multiplied by the time taken to repair a locus of MDx completely in the biomechanical sense. That "repair period" equals about 0.6 years in healthy human adults. When MDx production suddenly increases, the momentary MDx burden begins to increase too, and does so for a time equal to the repair period and in proportion to the increased MDx production. After the repair period elapses, the momentary MDx would tend to reach and stay at a maximum value as long as increased MDx production continued. Prolonging the repair period, preventing the creation of new remodeling units to repair MDx, or delaying mineralization of the new bone made by those units would also increase MDx burdens. Reducing MDx production or the repair period, or accelerating the creation of new modeling units would have the opposite effects on the momentary MDx burden but would also go through a transient phase before developing the new steady state conditions. Exploiting these relationships quantitatively and experimentally requires expressing them mathematically and using for the terms in any equations things one can define logically and measure practically. Accordingly, the article suggests a special definition of a unit amount of microdamage, how to measure it, and simple algebra and equations for calculating some effects of microdamage on the biologic system.

Algorithms↗
PubMed1989

Some effects of basic multicellular unit-based remodelling on photon absorptiometry of trabecular bone.

This article offers algorithms and an algebra for estimating effects of bone turnover, remodelling space, undermineralized bone and trabecular surface-to-volume ratio effects on trabecular bone mass estimation by photon absorptiometry. From published histomorphometric data and other evidence the algorithms suggest the amount of mineral in a given bone sample can suggest to absorptiometry an amount of bone that differs from the truth by over 40% in the extreme, and more commonly by 5-15%. They suggest that by reducing a bone's global mineral content high bone turnover causes underestimation of true bone mass. They suggest that by letting mineral return to the remodelling space and undermineralized bone, reduced bone turnover causes apparent gains in bone mass. The commonly suggested 5-15% magnitude of such errors exceeds those assumed in the past. The algorithms suggest that after a challenge to remodelling those bone mineral changes can take from 6 months to over 3 years to reach steady states. Those features could explain why many osteoporosis treatments judged effective from initial absorptiometric evidence failed when used for long periods in patients. Finally the algorithms suggest that a real increase in ideal bone volume can even appear to absorptiometry as no gain or an initial loss, which has already happened in two human experiments.

Bone Development↗